Currently, the phenomenal increase in the use of high throughput screening and genomic/proteomic arrays has brought about the necessity for manipulation of large numbers of different samples. In the case of arrays, thousands of different DNA samples are often “spotted” onto a support material. In general, the task is to pick up a small volume of liquid from a vessel and apply the volume of liquid to a surface, or disperse and mix the volume of liquid in another liquid containing vessel.
As the technology currently available for carrying out such tasks, the method and apparatus for forming microarrays of biological samples on a support are disclosed (Japanese laid-open publication No. 10-503841, U.S. Pat. No. 5,807,522). This method involves dispensing a known volume of a reagent at each selected array position, by tapping a capillary dispenser on the support under conditions effective to draw a defined volume of liquid onto the support. This method comprises; filling an aqueous solution of a selected analyte-specific reagent into a reagent-dispensing device having an elongate capillary channel adapted to hold a quantity of the reagent solution and having a tip region at which the solution in the channel forms a meniscus, tapping the tip of the dispensing device against a solid support at a defined position on the surface with an impulse effective to break the meniscus in the capillary channel and deposit a selected volume between 0.002 and 2 μl of solution onto the surface, and repeating the above steps until the microarray is formed.
Further, a method of performing array-based hybridization assays using thermal inkjet deposition of sample fluids is disclosed (U.S. Pat. No. 6,221,653, Japanese laid-open publication No. 11-187900). Furthermore, there is a method using pins and rings or slotted tip pins.
While such methods allow generation of arrays, they are hampered by a severe limitation.
In order to be re-usable, they must be washed between applications of different reagents. The washing step needed when sets of reagents are changed is a slow process that reduces throughput when generating arrays. In addition, if the washing step is not complete, there is possibility of cross-contamination, on the occasion of reusing the same tips.
Further, when the various proteins are treated as reagents, even if a washing step is included, there is a problem that proteins cannot be completely removed and re-using cannot be executed.
Furthermore, there is another problem in that the pins and jet components cannot be autoclaved during the manufacture of the arrays.
Consequently, the present invention aims to resolve the problems outlined above. A first object is to provide a samples delivering device, a method of manufacturing a samples applicator, a method of delivering samples, and a base activation device that allows manipulation of large numbers of different samples, efficiently and promptly.
A second object is to provide a samples delivering device, a method of manufacturing a samples applicator, a method of applying samples, and a base activation device that can be easily produced, the cost of production is reduced and the sample applicator is disposable, does not require washing, and has no contamination or carry-over concerns.
A third object is to provide a samples delivering device, a method of manufacturing a samples applicator, a method of delivering samples, and a base activation device that can be made in a sterile form for microbiological application.
A forth object is to provide a samples delivering device, a method of manufacturing a samples applicator, a method of delivering samples, and a base activation device that can efficiently and promptly manufacture arrays where a large number of samples are arranged.
A fifth object is to provide a samples delivering device, a method of manufacturing a samples applicator, a method of delivering samples, and a base activation device that have such a versatility that samples can be delivered without being restricted by shape, size, or type of the base.